The general purpose of this project is to investigate the roles of autonomic nervous system (ANS) activity, attention, and information processing and their interrelationships in the pathology, etiology, and prognosis of various psychiatric disorders. A second purpose is to determine biological and psychological processes related to ANS activity and attention. ANS activity is assessed by peripheral measures such as skin conductance, heart rate, and skin temperature. Subjects are tested under conditions of rest, presentation of tones, and performance on tasks such as reaction time, mental arithmetic, and memory. Biological mechanisms are investigated by correlating these variables with enzyme activity, neuropeptides, and levels of biogenic amines and their metabolites and with brain dysfunction as revealed by CT and PET scans. Recent and current work: 1) Schizophrenic patients are compared to controls and patients with affective and anxiety disorders, and we are studying the effects of a conventional neuroleptic drug, fluphenazine with the newer drug, clozapine, in comparison to placebo. Clozapine markedly attenuated ANS activity compared to both other treatments and had about the same effect on attention as the neuroleptic. 2) Young adult offspring of patients with bipolar affective disorder, who are at risk for developing an affective disorder, did not show the low ANS activity commonly seen in symptomatic depressives, but they were hyperresponsive in skin conductance reactions to mild stress, and these showed atypical lateralization. These subjects also showed an atypical subjective response to stress -- self-ratings of depression increased along with a normal increase in anxiety and they showed atypically strong correlations between state and trait anxiety and ANS activity not seen in controls. The results support a sensitization model of the development of affective disorders. 3) A study of the relationships of parental 'Expressed Emotion', an index of criticism and/or overinvolvement, and of parental diagnosis with ANS activity in children and adolescents who have obsessive-compulsive disorder. Parental expressed emotion, especially in fathers, is related to high skin conductance activity in these children.